Typically, oral dosage forms for the delivery of pharmaceutically active agents or drugs release the agent during passage through the gastrointestinal tract. The part of the gastrointestinal tract to which the active agent is delivered depends in part on the type of delivery system involved. Certain delivery systems release the active substance rapidly, leading to, for example, a rapid rise to a maximum concentration of drug in the blood usually followed by a rapid decrease in concentration as the drug is cleared from the body. If the drug concentration rises and/or decreases rapidly, this may create a narrow window of time during which the drug is therapeutically effective. As a result, sustained therapeutic efficacy may require administration of multiple, sequential doses of the drug. In addition, if release of drug to the body is uncontrolled in this manner, adverse events associated with the drug may not be controllable and the drug may not be effectively delivered to the site requiring treatment.
Various compositions and dosage forms have been used to control drug release and thereby provide sustained release of active agents to provide sustained efficacy from one composition. For example, a well-known way of controlling the release of drug is to apply a coating to a solid core. For example, a polymer coating can produce a rate controlling film on the surface of the core. The release rate of the therapeutic agent can then be altered by factors including the thickness of the coating, the diffusivity of agent, through the coating, and the rate of biodegradation of the coating. If the coated dosage form is broken, or damaged, during or after administration, the coating may no longer provide an effective rate controlling film resulting in the drug being rapidly released from the core.
Drug dosing regimens, be they acute or chronic, may vary from patient to patient. Different patients can have different therapeutic responses to a given dose of drug. Further, physicians sometimes start with a smaller than recommended dose of a drug and titrate the dose upward over time to minimize, for the patient, the frequency and severity of adverse events associated with optimum blood concentrations of the drug. Alternatively, for some patients and/or drug therapies, physicians start with a high, or loading dose of drug to achieve maximum and rapid therapeutic benefit and then reduce the dose administered to maintain efficacy. Such dosing regimens require precise control over the dosage administered, which, with the right formulation, can be achieved using for example, a single tablet that may be sub-divided into subunits each having a smaller dose of the drug, where each of the subunits delivers the drug in the same manner as the tablet from which they were derived.
There is a need, therefore, for a formulation of a pharmaceutically active agent, which when sub-divided or broken into smaller dosage forms achieves substantially the same sustained release profile as the original formulation, and which conveniently permits modification of dosing regimens.